Functionally Distinct Transmission of Human Immunodeficiency Virus Type 1 Mediated by Immature and Mature Dendritic Cells

Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Journal of Virology (Impact Factor: 4.65). 10/2007; 81(17):8933-43. DOI: 10.1128/JVI.00878-07
Source: PubMed

ABSTRACT Dendritic cells (DCs) potently stimulate the transmission of human immunodeficiency virus type 1 (HIV-1) to CD4(+) T cells. Immature DCs (iDCs) located in submucosal tissues can capture HIV-1 and migrate to lymphoid tissues, where they become mature DCs (mDCs) for effective antigen presentation. DC maturation promotes HIV-1 transmission; however, the underlying mechanisms remain unclear. Here we have compared monocyte-derived iDCs and mDCs for their efficiencies and mechanisms of HIV-1 transmission. We have found that mDCs significantly facilitate HIV-1 endocytosis and efficiently concentrate HIV-1 at virological synapses, which contributes to mDC-enhanced viral transmission, at least in part. mDCs were more efficient than iDCs in transferring HIV-1 to various types of target cells independently of C-type lectins, which partially accounted for iDC-mediated HIV-1 transmission. Efficient HIV-1 trans-infection mediated by iDCs and mDCs required contact between DCs and target cells. Moreover, rapid HIV-1 degradation occurred in both iDCs and mDCs, which correlated with the lack of HIV-1 retention-mediated long-term viral transmission. Our results provide new insights into the mechanisms underlying DC-mediated HIV-1 transmission, suggesting that HIV-1 exploits mDCs to facilitate its dissemination within lymphoid tissues.

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    • "Maturation stimulus HIV - 1 uptake Productive HIV - 1 infection Transmission of HIV - 1 to target CD4 + T cells References None ( immature DCs ) + ++ + Dong et al . ( 2007 ) and Wang et al . ( 2007b )"
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    • "In agreement with this scenario, it was reported that HIV is routed towards the infectious synapse in a surface accessible, intracellular compartment (Yu et al., 2008). Irrespective of the route of HIV trafficking, there is ample evidence that HIV capture does not preserve viral infectivity (Turville et al., 2004; Nobile et al., 2005; Burleigh et al., 2006; Wang et al., 2007a), with the initially postulated conservation of viral infectivity likely being due to productive infection of the transmitting cells (Nobile et al., 2005; Burleigh et al., 2006). Collectively, HIV trans-infection driven by dendritic cells is short lived (hours) and DC-SIGN on immature dendritic cells contributes to this process in at least two ways: DC-SIGN promotes capture and potentially uptake of virions subsequently transferred to T cells. "
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